title: Altered microRNA expression associated with reduced catecholamine sensitivity in patients with chronic heart failure.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF.
  
  
  RESULTS
  Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 μg kg(-1)min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ΔLV dP/dt(max)). These are Group I (n=7) with ΔLV dP/dt(max)>90%, and Group II (n=7) with ΔLV dP/dt(max)<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p<0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups.
  
  
  CONCLUSIONS
  Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Funahashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirashiki
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Yasuya
authors.initials: Y
authors.lastname: Inden
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D006328:Cardiac Catheterization; D002311:Cardiomyopathy, Dilated / Q000150:complications; D002395:Catecholamines / Q000502:physiology*; D002908:Chronic Disease; D004280:Dobutamine; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D046228:Microarray Analysis; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000737:chemistry; D009638:Norepinephrine / Q000097:blood; D011941:Receptors, Adrenergic / Q000502:physiology; D016276:Ventricular Function / Q000502:physiology
chemical_list: D002395:Catecholamines; D035683:MicroRNAs; D011941:Receptors, Adrenergic; D004280:Dobutamine; D009638:Norepinephrine